| Hydrogen sulfide (H2S) has recently been proposed as the thirdendogenous gasotransmitter which was similar to two other vasoactive gases,nitric oxide (NO) and carbon monoxide (CO). It is produced bypyridoxal-5'-phosphate-dependent enzymes, including cystathionine-γ-lyase(CSE), cystathionine-β-synthase (CBS), and3-mercaptopyruvate sulfurtransferase (3-MST). Recent research showed that H2S may play a variety ofbiological effect in the cardiovascular system, which may include regulatingvascular tone, decreasing blood pressure, protecting myocardium from theischemia-reperfusion myocardial injury, inhibiting the proliferation of thesmooth muscle cells. Hypertension is a serious cardiovascular disease whichmay lead to the incidence of myocardial infarction, stroke and chronic renalfailure. In hypertensive animals models, the plasma concentration of hydrogensulfide decreased. Renovascular hypertension is a common secondaryhypertension caused by renal arteries stenosis, finally will lead to ischemicnephropathy and with advanced kidney disease. The renin-angiotensin system(the renin-angiotensin system, RAS) was stimulated and its main activepeptide angiotensin II (angiotensin II, Ang II) increased in renovascularhypertension. A lot of research have proved the effects of Ang II includingconstrict vascular smooth muscle, increase arterial blood pressure, promotealdosterone secretion and sodium retention, promote cell division andproliferation, cause tissue reconstruction, which leading to a further increaseof blood pressure. Ang II play a biological role by acting with its receptors,mainly presenting in vascular smooth muscle, brain, heart and kidney. Theangiotensin II type1receptor (angiotensin type1receptor, AT1R) is the majorreceptor which mediated the vascular effect of Ang II.Hydrogen sulfide as an endogenous vasodilator factor plays an important role in the pathophysiological processes of hypertension. It has been provedthat the lacking of endogenous hydrogen sulfide can lead to hypertension.Endogenous H2S may play an antihypertensive role by directly relaxing bloodvessels, inhibiting the proliferation of vascular smooth muscle cells andslowing the vascular extracellular matrix remodeling. Research suggests thatconcentration and the formation rate of plasma hydrogen sulfide wassignificant reduced in renovascular hypertension. The expression of CSE genewhich is closely related to hydrogen sulfide synthesis was inhibited, andactivity was decreased; plasma hydrogen sulfide content and the formationrate and CSE activity were significantly elevated and blood pressure wasdecreased significantly after injecting hydrogen sulfide donor sodiumhydrosulfide (NaHS) to hypertensive rats. The role of H2S in modulating thethoracic aorta tension during prevention of blood pressure is still yet clear, theaim of this study was to explore the effects of H2S on thoracic aorta tensionand the underlying mechanism involved in renovascular hypertensive rats.Objective: To study the modulation effects of NaHS on the tension of theisolated thoracic aorta during the formation of renovascular hypertension.Methods:18seven-week-old male Sprague-Dawley rats were randomlydivided into3groups: sham group, two-kidney-one-clip group (2K1C group),2K1C+NaHS group. In the2K1C+NaHS group, the rats were injectedintraperitoneally with NaHS (56μmol/kg) daily from the three days after the2K1C operation. The sham group and2K1C group were injected with thesame dose of normal saline. The systolic blood pressure (SBP) was measuredbefore the operation and each week thereafter with a noninvasive tail-cuffplethysmograp. After4weeks, remove the thoracic aorta for (1) the tension ofthe thoracic aorta: using the method of isolation vascular ring perfusion, toexploration the Ang II (10-1010-6mol/L) induced vasocontraction of theisolated aortic rings and acetycholine (ACh,10-810-4mol/L) inducedendothelial dependent vasorelaxation, Sodium Nitroprusside(SNP,10-910-6mol/L) induced endothelial independent vasorelaxation.(2) western blot wasused to determine the protein expression of AT1R protein in thoracic aorta.(3) thoracic aortic malondialdehyde (MDA) was studied by thiobarbituric acidmethod.(4) the activity of SOD in thoracic aortic were detected.(5) Theplasma concentration of angiotensin II (Ang II) and H2S were studied as well.Results:1. The tail arterial pressure and the plasma concentration of AngII in2K1C group were significantly higher than those in sham group, butcompared with sham group, the plasma concentration of H2S was decreased,indicating that administration of NaHS markedly lowered rats tail arterialpressure, decreased the Ang II concentration in plasma, increased the plasmaconcentration of H2S.2. Ang II (10-1010-6mol/L)dose-dependently inducedvascular contraction in all groups. Ang II induced contraction of aortic rings in2K1C group was higher than that in sham group and were significantlydifferent in AngII concentration from10-8mol/L to10-6mol/L; compared with2K1C group, NaHS (56μmol/L) supplementation decreased the response toAng II of thoracic aorta (15.40±2.68%vs.21.52±2.45%, P<0.05;16.16±4.23%vs.34.23±6.47%, P<0.05). Ang II induced contraction ofthoracic aortic ring in all groups were inhibited by Losartan (the antagonist ofAT1receptor)30min incubation.3. In2K1C group, the relaxation of thoracicaorta to ACh (10-810-4mol/L) decreased compared with sham group(100.21±0.33%vs.50.76±3.67%, P<0.05) and the relaxation of thoracic aortato ACh in NaHS group increased to64.82±9.42%from50.76±3.67%compared with2K1C group (P<0.05); there were no significant differences inendothelium-independent relaxation induced by SNP in all groups.4.According to the western blotting results, AT1R protein expression wasupregulated in the2K1C group as compared with sham group, AT1R proteinexpression was reduced in NaHS group compared with2K1C group (P<0.05).5. The content of MDA in thoracic aortic rings were notably increased in2K1C group and was reduced in2K1C+NaHS group (P<0.05).6. Comparedwith sham group, the activity of SOD in thoracic aorta was significantlydecreased in2K1C group (P<0.05). The activity of SOD in2K1C+NaHSgroup was significantly higher than that in2K1C group(P<0.05)．Conclusion: Chronically administration of NaHS can decrease blood pressure in renovasocular hypertensive rats. The antihypertensive effect ofH2S were associated with decreased plasma Ang II level, downregulation ofAT1R protein expression in thoracic aotra and antioxidant activity of H2S. |
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